GAS8

Rationale: Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial

Refs: 26387594

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GAS8 variants in ClinVar

2 Conditions Cataloged

Primary ciliary dyskinesia 33Total: 8

GAS8-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	69 clinvar	9 clinvar	79
missense			142 clinvar	11 clinvar	5 clinvar	158
nonsense	6 clinvar		1 clinvar			7
start loss			1 clinvar			1
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	8	4	146	80	14	252

Highest pathogenic variant AF is 0.0000197081

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 0 of 0 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
No transcripts match your selected source or search query.

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
gas8	Danio rerio	Structure: slow muscle cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

gas8

Danio rerio

Structure: slow muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epithelial cilium movement
determination of left/right symmetry
brain development
negative regulation of cell population proliferation
flagellated sperm motility

Molecular Function

molecular_function
protein binding
microtubule binding
Rab GTPase binding

Cellular Component

Golgi apparatus
microtubule
cilium
axoneme
motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268699
Coding exons: 11
Length: 25347
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.919	339	295	1.15	0.0000193	3137
Missense (PolyPhen)		83	75.57	1.0983		767
Synonymous	-0.539	128	120	1.06	0.00000787	873
Loss of Function	0.817	21	25.4	0.825	0.00000133	301

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the nexin-dynein regulatory complex (N- DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper motile cilia functioning (PubMed:26387594, PubMed:27120127, PubMed:27472056). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by faciltating the trafficking of SMO into the cilium and the stimulation of SMO activity in a GRK2-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q60779, ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:26387594, ECO:0000269|PubMed:27120127, ECO:0000269|PubMed:27472056}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.778
RVIS EVS: 0.21
RVIS percentile EVS: 67.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.919

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium